Deregulation of p27 and Cyclin D1/D3 Control Over Mitosis Is Associated with Unfavorable Prognosis in Non-small Cell Lung Cancer, as Determined in 405.

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Deregulation of p27 and Cyclin D1/D3 Control Over Mitosis Is Associated with Unfavorable Prognosis in Non-small Cell Lung Cancer, as Determined in 405 Operated Patients William Sterlacci, MD, Michael Fiegl, MD, Wolfgang Hilbe, MD, Herbert Jamnig, MD, Wilhelm Oberaigner, MD, Thomas Schmid, MD, Florian Augustin, MD, Jutta Auberger, MD, Ellen C. Obermann, MD, Alexandar Tzankov, MD Journal of Thoracic Oncology Volume 5, Issue 9, Pages 1325-1336 (September 2010) DOI: 10.1097/JTO.0b013e3181e77efc Copyright © 2010 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 1 Signaling pathways of the epidermal growth factor receptor. EGFR, epidermal growth factor receptor; EMT, epithelial–mesenchymal transition; pAkt, phosphorylated Akt; PTEN, phosphatase and tensin homologue; pSTAT3, phosphorylated signal transducer and activator of transcription 3; PI3K, phosphatidylinositol-3′ kinase; β-cat, β-catenin; E-cad, E-cadherin; PIP2, phosphatidylinositol-4,5-bisphosphate; PIP3, phosphatidylinositol-3,4,5-trisphosphate; EMT, epithelial–mesenchymal transition; CCND1, cyclin D1 gene. Journal of Thoracic Oncology 2010 5, 1325-1336DOI: (10.1097/JTO.0b013e3181e77efc) Copyright © 2010 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 2 Immunohistochemical expression of cyclin D1 (A), cyclin D2 (B), cyclin D3 (C), cyclin E (D), p21 (E), nuclear p27 (F), cytoplasmic p27 (G), phosphorylated signal transducer and activator of transcription 3 (H), phosphorylated Akt (I), membranous β-catenin (J), nuclear β-catenin (K), E-cadherin (L), epidermal growth factor receptor (M), Snail (N), phosphatidylinositol-3′ kinase (O), and phosphatase and tensin homologue (P) in non-small cell lung cancer tissue microarray samples. Original magnification ×400. Journal of Thoracic Oncology 2010 5, 1325-1336DOI: (10.1097/JTO.0b013e3181e77efc) Copyright © 2010 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 3 Fluorescence in situ hybridization analysis for epidermal growth factor receptor (EGFR) (A) and Cyclin D1 (CCND1) genes (B, C). (A) Note highly increased numbers of red (EGFR) compared with green signals (centromere 7) corresponding to high-level amplification. (B) Note increased, but balanced red (telomeric) and green (centromeric) signals in tumor cells, due to amplification of doubled-colored probes flanking CCND1, corresponding to high amplification of CCND1. (C) Note split red (telomeric) and green signals (centromeric) as well as increased red signals corresponding to unbalanced translocation involving the CCND1 locus on chromosome 11 with double minutes of the telomeric parts of the chromosome. Journal of Thoracic Oncology 2010 5, 1325-1336DOI: (10.1097/JTO.0b013e3181e77efc) Copyright © 2010 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 4 Kaplan-Meier survival estimate graphs comparing cases above and below cutoff levels for E-cadherin (A), nuclear p27 (B), cyclin D3 (C), cyclin D1 (D), EGFR (E), and combination of E-cadherin and cyclin D3 (F). Journal of Thoracic Oncology 2010 5, 1325-1336DOI: (10.1097/JTO.0b013e3181e77efc) Copyright © 2010 International Association for the Study of Lung Cancer Terms and Conditions